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Andrade-Sousa, A.S.* ; Rogério Pereira, P.* ; MacKenzie, B.* ; Oliveira-Junior, M.C.* ; Assumpção-Neto, E.* ; Brandão-Rangel, M.A.* ; Damaceno-Rodrigues, N.R.* ; Garcia Caldini, E.* ; Velosa, A.P.* ; Teodoro, W.R.* ; Ligeiro de Oliveira, A.P.* ; Dolhnikoff, M.* ; Eickelberg, O. ; Vieira, R.P.*

Aerobic exercise attenuated bleomycin-induced lung fibrosis in Th2-dominant mice.

PLoS ONE 11:e0163420 (2016)

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Introduction: The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin-induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods: BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX); (n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results: At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1; p<0.01), (IL-1β; p<0.001), (IL-5; p<0.01), (IL-6; p<0.001), (IL-13; p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion: AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model.

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